We have studied the mechanisms by which HIV-1 Tat and HTLV-I Tax proteins activate transcription. Recent findings relevant to the HIV-1 system include the following: 1) The Tat-responsive element in the TAR RNA has been better defined. Besides the commonly recognized bulge element, we have recently demonstrated that the stem sequences immediately flanking the bulge are also important. This finding has been independently confirmed by two other laboratories. 2) The DNA target in the LTR for Tat response has been more precisely characterized. In particular, it is increasingly clear that the Sp1 elements and the particular HIV-1 TATAA box are very important for optimal trans-activation. 3) A second cellular TAR RNA-binding protein has been isolated. This protein has been identified as the human autoantigen La. For the HTLV-I system, we have characterized 47 different mutant Tax proteins. Results from this analysis have allowed us to define two different types of activation domains for Tax. The first is a domain necessary for interaction with the CREB/Ap1 pathway. The second is a domain involved in the NF-kappaB pathway. The former is presumably used for activation of the HTLV-1 LTR while the latter presumably account for Tax activation of the HIV-1 LTR. We have also designed and tested in vitro a ribozyme specific for the HIV-1 U5 sequence. Results here demonstrated that high expression of this ribozyme can functionally suppress productive HIV-1 production in CD4+ T-cells.